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Browsing by Author "Parodi, Luca"
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Item Distinct molecular pathways in ovarian endometrioid adenocarcinoma with concurrent endometriosis(Wiley, 2018) Zhang, Chi; Wang, Xiyin; Anaya, Yanett; Parodi, Luca; Cheng, Lijun; Anderson, Matthew L.; Hawkins, Shannon M.; Medicine, School of MedicineWomen with endometriosis, a benign growth of endometrial tissue outside the uterine cavity, are at increased risk of specific histotypes of epithelial ovarian cancer, such as ovarian endometrioid adenocarcinoma (OEA). Women with OEA who have endometriosis at time of surgical staging demonstrate improved clinical prognosis compared to women with OEA without evidence of endometriosis. However, the molecular contributions of the endometriotic tumor microenvironment to these ovarian cancers remain poorly understood. As a starting point, we used a platform for genome‐wide transcriptomic profiling to compare specimens of OEA from women with and without concurrent endometriosis and benign reproductive tract tissues, including proliferative endometrium and typical and atypical endometrioma samples (n = 20). Principle component analysis revealed distinct clustering between benign and malignant samples as well as malignant samples with and without concurrent endometriosis. Examination of gene signatures revealed that OEA with concurrent endometriosis contained a unique molecular signature compared to OEA without concurrent endometriosis, distinguished by 682 unique genes differentially expressed (fold change < or >1.5, p < 0.01). Bioinformatic analysis of these differentially expressed gene products using ingenuity pathway analysis revealed activation of NFkB signaling, an inflammatory signaling pathway constitutively active in endometriosis. DAVID functional annotation clustering further revealed enrichment in RAS signaling as both cytoskeleton organization and GTPase regulator activity relied heavily on RAS protein signal transduction. Gene set enrichment analysis highlighted immune and inflammatory nodes involved in OEA with concurrent endometriosis. These observations provide novel resources for understanding molecular subtleties potentially involved in OEA within the context of the endometriotic tumor microenvironment.Item Translational Applications of Linear and Circular Long Noncoding RNAs in Endometriosis(MDPI, 2021-09-30) Wang, Xiyin; Parodi, Luca; Hawkins, Shannon M.; Obstetrics and Gynecology, School of MedicineEndometriosis is a chronic gynecologic disease that negatively affects the quality of life of many women. Unfortunately, endometriosis does not have a cure. The current medical treatments involve hormonal manipulation with unwanted side effects and high recurrence rates after stopping the medication. Sadly, a definitive diagnosis for endometriosis requires invasive surgical procedures, with the risk of complications, additional surgeries in the future, and a high rate of recurrence. Both improved therapies and noninvasive diagnostic tests are needed. The unique molecular features of endometriosis have been studied at the coding gene level. While the molecular components of endometriosis at the small RNA level have been studied extensively, other noncoding RNAs, such as long intergenic noncoding RNAs and the more recently discovered subset of long noncoding RNAs called circular RNAs, have been studied more limitedly. This review describes the molecular formation of long noncoding and the unique circumstances of the formation of circular long noncoding RNAs, their expression and function in endometriosis, and promising preclinical studies. Continued translational research on long noncoding RNAs, including the more stable circular long noncoding RNAs, may lead to improved therapeutic and diagnostic opportunities.